类风湿关节炎患者血清炎性因子、ANCA水平与血管内皮损伤标志物的相关性分析

目的:探讨类风湿关节炎(RA)患者血清炎性因子及抗中性粒细胞胞浆抗体(ANCA)水平与血管内皮损伤的相关性。方法:106例RA患者,分为活动组(83例)和缓解组(23例),55例健康人群作为对照,采用ELISA检测各组血清炎性因子白介素-1β(IL-1β)、白介素-6(IL-6)、白介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)及血管内皮损伤标志物-血管性血友病因子(vWF)、可溶性细胞间黏附分子-1(sI-CAM-1)及血管内皮黏附分子-1(sVCAM-1)水平;采用间接免疫荧光法(IIF)检测各组血清ANCA阳性率。比较各组上述指标水平差异,分析两组RA患者炎性因子水平、ANCA阳性率与血管内皮损伤标志物水平的相关性。结果:RA活动组IL-6、TNF-α、vWF、sICAM-1、sVCAM-1血清水平均高于对照组(P<0.05);RA缓解组IL-6、vWF水平均低于RA活动组(P<0.05),但vWF、sVCAM-1水平仍显著高于对照组(P<0.01);RA患者IL-6、IL-1β、IL-17与血管内皮损伤标志物有不同程度的相关性;RA患者活动组ANCA阳性率为32.5%,显著高于对照组(P<0.01);ANCA阳性患者vWF水平高于ANCA阴性患者(P<0.05)。结论:RA活动期患者存在较明显血管内皮损伤,这种损伤与高水平的炎性因子及ANCA阳性表达有关。     

不同糖皮质激素应用途径治疗类风湿关节炎对患者肺部感染的影响分析

目的:探讨不同糖皮质激素应用途径治疗类风湿关节炎对患者肺部感染的影响。方法:2013 年1 月至2017年2 月选择在我院诊治的RA 患者128 例作为研究对象,根据随机信封抽签原则分为观察组与对照组各64 例,观察组给予关节腔注射糖皮质激素治疗,对照组给予口服糖皮质激素治疗,两组都治疗观察8 周。结果:观察组与对照组的治疗总有效率分别为96.9%和84.4%,观察组的治疗总有效率明显高于对照组(P<0.05)。观察组与对照组治疗后的关节疼痛与关节肿胀指数都明显低于治疗前(P<0.05),同时治疗后观察组的关节疼痛与关节肿胀指数也明显低于对照组(P<0.05)。观察组与对照组的肺部感染发生率分别为1.6%和7.8%,观察组的肺部感染发生率明显低于对照组(P<0.05)。观察组治疗后的CRP 与RF 值分别为(10.11±3.19)mg/ L 和(50.22±19.82)U/ ml,都明显低于对照组的(17.49±5.32)mg/ L 和(59.14±20.59)U/ ml(P<0.05),同时两组治疗后的CRP 与RF 值都明显低于治疗前(P<0.05)。结论:相对于口服治疗,关节腔内注射糖皮质激素治疗RA 能降低肺部感染发生率,抑制炎症因子与RF 表达,促进缓解临床症状,从而提高治疗效果。     

吸入性糖皮质激素治疗小儿支气管哮喘的临床疗效及对血清炎性因子的影响

目的:观察并分析吸入性糖皮质激素治疗小儿支气管哮喘的临床疗效及对血清炎性因子水平的影响。方法:选取本院2019-10—2021-10收治的急性期支气管哮喘患儿80例作为研究对象,随机分成对照组40例和观察组40例,对照组患儿实施常规治疗加孟鲁司特钠咀嚼片口服,观察组患儿在常规治疗的基础上辅以吸入性糖皮质激素治疗。治疗7天后,比较两组患儿临床疗效、临床症状改善时间以及治疗前后肺功能指标[第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、呼气峰流速(PEF)]和血清炎性因子指标[C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF-α)]水平变化及组间差异。结果:治疗7天后,观察组患儿总有效率为92.50%,显著高于对照组的72.50%(P<0.05)。观察组患儿哮鸣音消失时间、气促消失时间、咳嗽消失时间均显著短于对照组(P<0.05)。治疗后,两组患儿FEV1、FVC、PEF、CRP、IL-6、TNF-α水平均较治疗前改善,且观察组患儿改善效果均显著优于对照组(P<0.05)。两组患儿不良反应率比较差异无统计学意义(P>0.05)。结论:支气管哮喘小儿常规治疗辅以吸入性糖皮质激素治疗疗效更显著,且安全性高,值得临床推广应用。     

淫羊藿苷对RA滑膜细胞凋亡及炎性因子表达的影响及机制研究

为探讨淫羊藿苷(icariin,ICA)对RA成纤维细胞样滑膜细胞(fibroblast-like synoviocytes,FLS)凋亡及炎性因子表达的影响,并探讨其可能的作用机制,体外分离及培养人RA FLS,用MTT和克隆细胞形成试验分别检测ICA对RA FLS增殖活性及克隆形成能力的影响,ELISA检测FLS分泌炎性因子TNF-α、IL-6的水平,流式细胞术检测FLS的凋亡情况,Western blotting检测ICA对RA FLS中细胞周期蛋白D1(Cyclin D1)、裂解的半胱氨酸蛋白酶3(Cleaved Caspase-3)、B淋巴细胞瘤2基因(B-cell lymphoma 2,Bcl-2)、Bcl-2相关蛋白(Bcl-2-associated X protein,Bax)及磷脂酰肌醇激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)信号通路相关蛋白表达的影响。结果显示,LPS诱导FLS后,ICA对RA FLS的增殖率及细胞克隆形成能力均呈浓度依赖性抑制效应(P0.05);ICA不同剂量组与LPS组相比,TNF-α、IL-6分泌水平明显降低(P0.05),细胞凋亡率明显增加(P0.05),Cyclin D1、Bcl-2、磷酸化PI3K(phospho-PI3K, p-PI3K)、磷酸化AKT(phospho-AKT, p-AKT)表达明显降低(P0.05),而Cleaved Caspase-3、Bax表达明显升高(P0.05)。提示ICA可降低人RA FLS的增殖能力,诱导其凋亡,并可降低其炎性因子的表达,这可能与抑制PI3K/AKT信号通路活化有关。     

细胞焦亡相关因子在类风湿关节炎患者中的表达及意义

背景：类风湿关节炎是常见的自身免疫性疾病,主要侵犯机体关节部位,特征为持续性滑膜炎症,研究提示促炎性的细胞焦亡与类风湿关节炎疾病的发生发展密切相关。目的：明确类风湿关节炎患者血清和关节液中细胞焦亡相关因子NOD样受体蛋白3、半胱氨酸天冬氨酸蛋白酶1、白细胞介素18及白细胞介素1β的表达水平及其临床意义。方法：选择2021年1月至2022年1月河南省洛阳正骨医院(河南省骨科医院)风湿病科收治的类风湿关节炎患者24例(类风湿关节炎组),同期选取伴膝关节积液的骨关节炎患者30例(骨关节炎组),健康受试者40例(对照组)。检测并记录3组受试者的C-反应蛋白、红细胞沉降率、抗环瓜氨酸肽抗体、类风湿因子水平和类风湿关节炎28个关节疾病活动度评分。采用酶联免疫吸附法测定血清和关节液中NOD样受体蛋白3、半胱氨酸天冬氨酸蛋白酶1、白细胞介素18及白细胞介素1β的表达水平,分析上述4项因子表达水平与类风湿关节炎患者临床指标之间的相关性。结果与结论：(1)类风湿关节炎组患者血清中的NOD样受体蛋白3、半胱氨酸天冬氨酸蛋白酶1、白细胞介素18及白细胞介素1β水平显著高于对照组(P <0.000 1),...     

多发性肌炎/皮肌炎患者糖皮质激素治疗前后其受体的改变及意义

为了探讨多发性肌炎 /皮肌炎 (PM/DM )患者外周血白细胞糖皮质激素受体 (GCR )的变化与意义及应用糖皮质激素(GC)疗效的关系 ,应用放射配体结合法 ,以3H标记地塞米松 ( 3H Dex)为配体 ,测定 2 4例PM/DM患者应用激素治疗前后白细胞GCR的变化 ,同时采用放射免疫分析法测定血浆皮质醇浓度。结果表明PM/DM患者应用GC治疗前其GCR特异结合量 ( 3 673± 1195位点 /细胞 )低于正常对照组 ( 4 966± 12 10位点 /细胞 ) ,有显著性差异 (P <0 0 1)。应用GC治疗后 ,激素抵抗组其GCR降低幅度 ( 85 9± 10 8位点 /细胞 )高于激素敏感组降低幅度 ( 62 6± 12 7位点 /细胞 ) ,差异有显著性 (P <0 0 0 1)。PM/DM患者应用GC治疗前后其GCR水平与相对应的血浆皮质醇浓度之间 ,无相关性 (P >0 0 5 )。提示PM/DM患者外周血白细胞GCR水平的变化与PM/DM的发病机制、应用GC治疗的疗效判定、预测预后等可能有密切关系 ,GCR对于PM/DM合并恶性肿瘤患者的意义尚待进一步研究     

类风湿关节炎的诊断及内科治疗

类风湿关节炎（RA）是一种常见的全身性自身免疫病,目前尚无特异性诊断及治疗方法,尤其是不典型和特殊类型RA易于误诊误治。近年来,AKA、APF、抗RA33、抗CCP、抗Sa及抗BiP抗体等新型自身抗体的发现提高了RA诊断的敏感性和特异性;核磁共振、CT及超声检查等影像学检查提高了RA关节损害的检出率,这些新的血清学检测指标及影像学检查的应用有助于RA的早期诊断。与此同时,新的DMARDs和生物制剂不断问世,RA的治疗手段不断丰富。已经证实,绝大多数RA患者经过早期、联合、个体化的规范治疗,预后良好。     

类风湿因子及相关自身抗体对类风湿关节炎的诊断价值

目的探讨类风湿因子（RF）、抗环瓜氨酸肽抗体（抗CCP）及抗角蛋白抗体（AKA）联合检测对类风湿关节炎（RA）的临床诊断价值。方法对80例RA和65例非RA的其他自身免疫病患者检测RF、RF-IgM、抗CCP及AKA 4种指标。结果自身免疫性疾病女性发病较高,以RA组为甚;RA组的RF、RF-IgM、抗CCP及AKA高于其他自身免疫性疾病组;单指标检测RA诊断的敏感性为RF〉RF-IgM〉AKA〉抗CCP,特异性为RF-IgM〉抗CCP〉RF〉AKA。阳性预测值为抗CCP〉RF〉RF-IgM、AKA,阴性预测值为RF〉RF-IgM〉AKA〉抗CCP;以并联或串联方式联合检测均以RF、RF-IgM及抗CCP三联及RF、RF-IgM、抗CCP及AKA四联检测为佳,并联检测的敏感性分别为93%及97%,串联检测的特异性分别为98%及99%。结论 RF、RF-IgM、抗CCP及AKA 4种指标联合检测可提高对RA诊断的敏感性和特异性,对RA的早期诊断有较高价值。     

雷公藤及其提取物对类风湿关节炎免疫调节机制的研究进展

类风湿关节炎是一种以侵蚀性关节炎为主要表现的慢性全身性的自身免疫性疾病。目前病因尚不明确。我国传统中药雷公藤对类风湿关节炎有较好的疗效,一直是研究热点。本文综述近年来国内外以雷公藤及其提取物治疗类风湿关节炎的机制,并阐述研究现状。     

Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis

Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA.     

类风湿性关节炎患者T细胞亚群失衡与炎性粘附分子的关系

目的：探讨类风湿性关节炎（RA）患者细胞免疫调节功能异常与参与介导免疫炎性损伤的细胞粘附分子之间的关系。方法：以ELISA方法检测40例RA患者外周血中IL－2、IL－10、 sICAM-1、sVCAM-1水平。结果：RA患者TH1，细胞因子IL－2水平明显低于健康对照组；TH2细胞因子IL－10及细胞粘附分子sICAM-1/sVCAM-1水平明显高于健康对照组，各组间比较均具有显著性差异（P＜0．01）。结论：RA患者高水平的 IL－10与低水平的IL－2提示TH2细胞功能亢进，进而TH1细胞被抑制，并导致细胞因子谱的偏移；高水平的sICAM-1、sVCAM-1是RA患者慢性炎症损伤的重要介质；异常升高的IL－10与细胞粘附分子的共同作用是导致RA患者病理损伤的重要原因。     

Expression of aryl hydrocarbon receptor,inflammatory cytokines,and incidence of rheumatoid arthritis in Vietnamese dioxin-exposed people

Many Vietnamese citizens have been and continue to be inadvertently exposed to dioxins and dioxin-like compounds deposited in the country during the Vietnam War. Dioxins may be involved in the pathogenesis of inflammatory diseases in part via by affecting expression of aryl hydrocarbon receptor (Ahr) and inflammatory cytokines in animal models. As the role of the Ahr in dioxin-exposed people is not well defined, a study was conducted to examine gene expression levels of Ahr, inflammatory cytokines, and the incidence of diseases in dioxin-exposed citizens who had/still resided near a heavily dioxin-contaminated area in Vietnam. Whole blood from citizens at/around Da Nang airbase and control individuals living in unsprayed areas was collected. Serum levels of dioxins were analyzed by using a dioxins-responsive chemical-activated luciferase gene expression bioassay. Gene expression of Ahr, interleukin (IL)-1β, TNFα, IL-6, and IL-22 in whole blood was examined by quantitative real-time PCR. The results showed levels of dioxins and expression of Ahr, IL-1β, TNFα, and IL-6 were up-regulated while IL-22 expression was down-regulated in dioxin-exposed people. Various disease incidences in the study subjects was also examined. Interestingly, the incidence of rheumatoid arthritis (RA) in these individuals was increased compared to the estimated prevalence of this disease in the general Vietnamese population. Analyses also showed that expression levels of Ahr correlated to those of IL-6 and IL-22 in the dioxin-exposed people. Taken together, dioxins might be involved in an up-regulated expression of Ahr that might possibly relate to changes in level of inflammatory cytokines and, ultimately, in the incidence of select diseases in residents of Vietnam who had/continue to live near a dioxins-contaminated site.     

Intracytoplasmic Th1 and Th2 cytokines in rheumatoid arthritis blood and synovial tissue

In rheumatoid arthritis (RA), T cells have been proposed either as a main actor or as an epiphenomenon in such a primarily synoviocyte-driven disease. A major issue remains the remarkable paradox between the T cell infiltrate and the relative failure to detect definite markers of their activity. To determine the Th1/Th2 cytokine profile in RA synovium, we used a single cell flow cytometric assay for interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4 and IL-10 in paired peripheral blood (PB) and synovial tissue (ST) lymphocytes from RA and osteoarthritis (OA) patients and PB lymphocytes from healthy controls. Cytokines were undetectable in unstimulated PB and ST lymphocytes. More stimulated PB and ST CD4(+)lymphocytes produced IFN-gamma than IL-4, for all individuals tested. RA PB CD4(+)lymphocytes showed the same Th1 cytokine pattern as normal controls. No increase of such a Th1 profile was observed for ST lymphocytes. A specific recruitment of T CD4(+)lymphocytes in the rheumatoid inflamed synovium could not be concluded on the basis of these results.     

The role of T helper type 17 cells in inflammatory arthritis

While T cells have been implicated in the pathogenesis of inflammatory arthritis for more than three decades, the focus on the T helper type 17 (Th17) subset of CD4 T cells and their secreted cytokines, such as interleukin (IL)‐17, is much more recent. Proinflammatory actions of IL‐17 were first identified in the 1990s, but the delineation of a distinct Th17 subset in late 2005 has sparked great interest in the role of these cells in a broad range of immune‐mediated diseases. This review summarizes current understanding of the role of Th17 cells and their products in both animal models of inflammatory arthritis and human immune‐driven arthritides.     

The type I IFN system in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterized by joint inflammation, immune cell infiltration of the synovia, and cartilage/bone destruction. Despite noteworthy progress in the treatment of RA in recent years, many patients remain refractory to current therapeutic strategies that target either the adaptive immune system or mediators of the innate system. Type I interferons (IFNs) play a significant role in regulation of the innate immune system, originally being discovered as part of intracellular immune defence against viral infection. IFNs are pleiotropic cytokines, mediating both immunostimulatory and immunosuppressive effects. IFN-alpha and beta have been detected in RA synovial fluid and tissue and subsequent therapeutic approaches using type I IFN in murine models of arthritis and in human RA have produced different and controversial results. Great interest has been directed toward principally plasmacytoid dendritic cells (pDCs), although also toward myeloid dendritic cells, as sources of type I IFN. Furthermore, manipulation of DC populations in murine RA models demonstrated that pDCs could suppress the development of arthritis and autoimmunity and may offer an attractive therapy for T-cell-mediated autoimmune diseases. Finally, dendritic cells (DCs) are vehicles for the delivery of therapeutic vaccines, and clinical trials are ongoing in RA with “tolerogenic” DC populations. Further, studies on animal models of RA will elucidate how IFN and DCs contribute to the establishment of autoimmune arthritis and the potential for manipulation of these cell populations and products to re-establish the immune tolerance.     

Analysis of the cellular infiltrates and expression of cytokines in synovial tissue from patients with rheumatoid arthritis and reactive arthritis

The cellular infiltrates and cytokine patterns in synovial tissue (ST) from patients with rheumatoid arthritis (RA) and reactive arthritis (ReA) were compared in order to determine the mechanisms responsible for the chronic and destructive course of RA. Since the results could be influenced by differences in disease duration, ST was studied from patients in both early and late stages of the disease. Ten patients had early RA (<1 year), ten long-standing RA (>1 year), six early ReA (<1 year), and five long-standing ReA (>1 year). Histological analysis demonstrated that the scores for infiltration by lymphocytes and plasma cells, and the scores for inflammation, were significantly higher in RA than in ReA. Immunolabelling studies showed that in particular, the scores for infiltration by CD38+ plasma cells, granzyme B+ cells, and interferon-gamma (IFNγ)+ cells were significantly higher in RA than in ReA. The results were independent of the disease duration. The increased number of lymphocytes, plasma cells, and granzyme B+ cells in rheumatoid synovial tissue supports the paradigm that RA is the result of specific immune recognition in the joint and that granzyme B+ cells play an important role in joint destruction. © 1998 John Wiley & Sons, Ltd.     

Allergic manifestations in patients with rheumatoid arthritis

A functional dichotomy between Th1- and Th2-type immune responses has been suggested. This study was performed to investigate whether rheumatoid arthritis (RA), a disease with indications of Th1-deviated immune activation, is inversly related to atopic conditions which are Th2-mediated. Two hundred and sixty-three adult cases of RA, fulfilling the American Rheumatism Association (ARA) 1987 Revised Classification Criteria for RA, were identified in 1995 and compared with 541 randomly selected population referents. The presence of atopic manifestations was established through a postal questionnaire and by demonstrating circulating IgE antibodies to common allergens. RA was inversely associated with certain manifestations of rhinitis, which were regarded as the most reliable indicators of atopic disease in the present study. However, no negative association was seen between RA and asthma and eczema, respectively. The main results give some support for an inverse relationship between RA and rhinitis. The prevalence of circulating IgE antibodies was however similar in cases and controls, suggesting that the T-cell commitment mainly occurs in the affected organs.     

Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells

Acute inflammation is a complex and tightly regulated homeostatic process that includes leucocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro‐resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as rheumatoid arthritis (RA), it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive‐feedback regulatory pathways in a variety of cells, including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti‐inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets.     

Redox signalling and the inflammatory response in rheumatoid arthritis

Reactive oxygen species (ROS) are produced mainly during oxidative phosphorylation and by activated phagocytic cells during oxidative burst. The excessive production of ROS can damage lipids, protein, membrane and nucleic acids. They also serve as important intracellular signalling that enhances the inflammatory response. Many studies have demonstrated a role of ROS in the pathogenesis of inflammatory chronic arthropathies, such as rheumatoid arthritis. It is known that ROS can function as a second messenger to activate nuclear factor kappa-B, which orchestrates the expression of a spectrum of genes involved in the inflammatory response. Therefore, an understanding of the complex interactions between these pathways might be useful for the development of novel therapeutic strategies for rheumatoid arthritis.